The role of mu opoid receptors in diet-induced obesity

描述(由申请人提供)： 肥胖是北美最常见的营养障碍；当能量摄入大于能量消耗时，肥胖就会发展。饮食中的脂肪水平，以及食物的份量，被认为是促进肥胖人数的主要因素。这强调了有必要了解不仅调节食物摄入量，而且调节对脂肪的高度偏好的因素。在大量影响食物摄入量的多肽、神经递质和受体群体中，只有几个被证明能使动物吃得过多，并增加它们对脂肪的偏好。这份名单中包括Mu阿片受体。MU阿片受体使动物过量进食并增加对高脂肪饮食的偏好的确切机制(S)尚不清楚。已知的是，在肥胖动物中，这种受体种群在中枢神经系统中与摄食行为有关的多个区域显著增加。我们假设，在肥胖动物中观察到的暴饮暴食和脂肪偏好增加是阿片受体增加的原因之一。这项应用的目的是确定1)是什么导致肥胖症动物的u阿片受体增加；2)u阿片受体使阿片肥大和增加脂肪偏好的潜在机制；3)u阿片受体增加是否加强肥胖的发生。从研究中获得的结果可以提供一个潜在的靶点，以减轻在肥胖人群中观察到的暴饮暴食和脂肪偏爱增加。我们的研究计划将使用多学科方法，允许K01职业发展奖的候选人在检验中心假设的同时学习几种技术。研究计划的每一个方面都将在宾宁顿生物医学研究中心(洛杉矶巴吞鲁日)进行。赞助商(George A.Bray博士)和联合赞助商(伊丽莎白·弗洛伊德博士、Gerlinda Hermann博士和Richard Rogers博士)以及高度互动的基础和临床研究环境，将为候选人提供一个极好的培训机会，帮助她转变为一名成功的独立研究人员。 与公共健康相关：肥胖症每年造成约10万至30万人死亡，使其成为美国仅次于吸烟的第二大死因。这一应用将为肥胖的原因提供新的见解，并为帮助缓解这种疾病的发展提供一个靶点。

DESCRIPTION (provided by applicant): Obesity is the most common nutritional disorder in North America; it develops when energy intake is greater than energy expenditure. The level of fat in the diet, together with portion size, is thought to play a major role in promoting the number of individuals who are obese. This emphasizes the need to understand the factors that are involved in modulating not only food intake but also the high preference for fat. Of the large number of peptides, neurotransmitters, and receptor populations that affect food intake, only a few have been demonstrated to make animals overeat and increase their fat preference. Included in this list are mu opioid receptors. The precise mechanism(s) by which mu opioid receptors make animals overeat and increase the preference for a high fat diet is unknown. What is know [sic] is that in obese animals, this receptor population is significantly increased in multiple areas of the central nervous system that are known to be involved in feeding behavior. We hypothesize that the increased mu opioid receptors are contributing to the overeating and increased fat preference that is observed in obese animals. The goals of this application are to determine 1)what causes mu opioid receptors to increase in obese animals; 2)potential mechanisms by which mu opioid receptors make aniamls [sic] hyperphagic and increase fat preference; 3)if increased mu opioid receptors potentiates the development of obesity. The results obtained from the studies can provide a potential target to attenuate the overeating and increased fat prefrence [sic] that is observed in humans that are obese. Our research plan will use a multi-disciplinary approach to allow the candiate [sic] of this K01 career development award to learn several techniques while testing the central hypothesis. Each aspect of the research plan will be conducted at Pennington Biomedical Research Center (Baton Rouge, LA). The sponsor (Dr. George A. Bray) and co-sponsors (Drs. Elizabeth Floyd, Gerlinda Hermann and Richard Rogers) along with a highly interactive basic and clinical research environment, will offer the candidate a great training opportunity to facilitate her transition into becoming a successful independent investigator. PUBLIC HEALTH RELEVANCE: Obesity accounts for approximately 100,000 to 300,000 deaths a year, making this disease the second-leading cause of death in the United States second only to smoking. This application will provide new insights into the cause of obesity and provide a target to help alleviate the development of this disease.